In a Thursday morning press conference at San Francisco Municipal Transportation Agency headquarters, Lee called the incidents "the consequences of total irresponsibility. We cannot have that in our city."
He said the city's Vision Zero program to eliminate traffic deaths is showing progress and vowed to work along with groups representing pedestrians, cyclists and seniors to get the city to "come together even stronger to reinforce the standards of using our streets appropriately."
Lee returned repeatedly to the suggestion that individuals driving on city streets are not behaving responsibly.
"As much as we are doing to educate the public, whether it's through signage, through education, we have to also do a level of enforcement to hold these individuals accountable and make sure that they are using our streets safely," Lee said. "These are totally avoidable tragedies. Totally avoidable."
Chris Cassidy, the communications director for the San Francisco Bicycle Coalition, called the Wednesday night fatalities "an unprecedented night of tragedy for people biking in San Francisco."
But he added that Lee's remarks fail to address the ongoing death toll, which according to city statistics includes 110 pedestrians killed in traffic collisions since July 2010.
"I think what we heard this morning from city leaders was hollow words without any detail," Cassidy said. "The people of San Francisco deserve safer streets. That's the end of the discussion. They deserved them yesterday, and they deserve urgent steps and specific plans today by city leaders to deliver safer streets as soon as humanly possible."
The bike coalition noted that the sites of Wednesday fatalities, on John F. Kennedy Drive in Golden Gate Park and at Seventh and Howard streets South of Market, are located in high-injury corridors identified by the San Francisco Department of Public Health. The coalition and other street safety advocates have called for the creation of more protected bike lanes -- lanes that are physically separated from motorized traffic -- to help prevent collisions.
"We need to see protected bike lanes across San Francisco," Cassidy said. "We need to see them on JFK Drive, where they could have prevented the fatality that occurred yesterday. We need to see them in SoMa, which is a neighborhood crisscrossed by high-injury corridors."
The coalition released a list of more than 60 streets identified as high-injury corridors that the city has no immediate plans to make safer.
SFMTA chief Ed Reiskin appeared at Lee's press conference and agreed that the city's most dangerous locations and the causes of most accidents are well known.
"We know why they're happening, we know where they're happening, and we know what things we can do to make them least likely to happen," Reiskin said.
He said that change is coming to the most hazardous locales -- including Seventh and Howard, where one of Thursday's victims was killed by a driver who reportedly ran a red light.
Reiskin said that crosswalks were recently upgraded to make pedestrians more visible to drivers and that traffic signals have been mounted on long arms across the intersection where motorists can see them more easily.
"Last night's episode showed design alone isn't sufficient if somebody is speeding through the streets and disobeying the laws," Reiskin said.
San Francisco police are investigating two hit-and-run collisions on Wednesday evening in which motorists struck and killed cyclists, then fled.
NBC Bay Area reports details of the first incident, which took place about 6 p.m. on John F. Kennedy Drive near 30th Avenue. A woman riding her bike there was struck by a white Honda Fit:
Witnesses said the vehicle was traveling about 50-60 mph when it crossed over into oncoming traffic to pass another vehicle and hit the bicycle head-on.
"I heard an impact, and I look and see the woman who had just passed us fly up, and I saw the bike fly the other direction," said Timmory Johnson.
Witnesses said the driver slowed momentarily after the impact then took off in a hurry.
The woman, in her 20s, was not responsive at the scene, despite the efforts of emergency crews to revive her. She was taken to a hospital, where she was pronounced dead.
The vehicle, which had paper dealership plates, was found a few blocks away with a shattered windshield. Police said at least two people were in the vehicle, and they are searching for a second vehicle that may lead them to the person or persons responsible.
The second fatal collision occurred about 8:30 p.m. at Seventh and Howard streets in the SoMa neighborhood. In that incident, witnesses said, a driver ran a red light, struck a female cyclist, and drove on.
Police say they were able to locate and arrest the driver, apparently after other cyclists spotted the male driver just blocks west of the collision scene.
According to a post on Reddit's San Francisco subreddit, the driver was seen trying to walk away from his vehicle after a second collision, this time with another vehicle:
I saw a man flee a car with airbags opened and signs of a fresh accident, as the car hit into another car. Called 911 and tried to get the attention of other driving passerbys that paused but kept going. As the guy tried to blend in with others on the street, I chased him down with another pedestrian and demanded he sit and wait for the police, he obliged. Definitely not sober. F'ing guy killed someone due to his recklessness. Witnesses said he blew through a red light when he struck the girl. His car told the same story.
Neither the woman killed in Golden Gate Park nor the one killed South of Market had been identified as of early Thursday. According to an unofficial list of cyclists killed in San Francisco (h/t HoodlineSF), Wednesday's fatalities were the 14th and 15th since 2011.